Culture tools, such as, for example, dishes, plates, flasks, and other types of vessels, are widely used in the laboratory for a variety of purposes. In normal use, cell and tissue culturing involves the use of agar or medium, which covers the bottom of a well. Cells are routinely cultured in research laboratories for basic biochemical and cell biology research to further understand natural biological processes. Recently, cell culture systems have been used in drug discovery and development in order to test for pharmacological and toxicological effects of drug candidates. This work generally is a monoculture test process, i.e., cells of one type are grown in a suitable medium in a tissue culture vessel such as a well, a plate, or a flask.
A normal cell culture plate consists of a chamber with a flat bottom surrounded by vertical walls to allow filling of the chamber with liquid and a removable cover to retain humidity and to protect against contamination. As shown in FIGS. 1A and 1B, a commonly used multi-well plate 100 has six identical wells 110. Although the wells 110 can be formed integrally, as by injection or blow molding for example, a preferred method of manufacture is to form the plate 100 with an upper tray 120 which defines the volume contained in each well and a lower or bottom tray 130 which defines the bottom surface of each well. The well 110 depth, together with the diameter of the well 110, determines the fluid capacity of each well 110. Typically for example, each well 110 in a six well plate is about 0.35 cm. in diameter and 2.0 cm. deep, and the wells are preferably arranged in a 2 by 3 regular rectangular array.
As shown in FIG. 1B, cells 140 are deposited in the bottom of each of the wells 110. A fluid 150 is then added to cover the cells 140.
Cell culture systems, commonly known as in vitro systems, are used extensively in drug discovery and development for the evaluation of drug properties. For instance, cell culture systems are used to evaluate drug efficacy, drug metabolism, or drug toxicity. However, it is also recognized that an in vitro system may not accurately predict in vivo effects due to the lack of the complexity and interplay of biological processes in in vitro systems. For instance, by using primary liver cells (hepatocytes) in culture, the effect of a substance on liver cells can be evaluated. However, in vivo, the substance may be metabolized by other organs such as the kidneys, and the resulting metabolite may have a different effect on liver cells which would not be detected by using liver cells alone. For this reason, interest has developed in the co-culture of cells. Co-culturing involves growing one population of cells in the presence of another population of cells. Cell co-culturing has been applied in a myriad of biological studies. In pharmacology and toxicology, co-culturing of a target cell, such as, for example, cancer cells, with cells from a critical organ, such as, for example, the liver, allows the evaluation of the effect of a chemical on the target cells after its modification by cells from the critical organ, such as, for example, liver metabolism of a specific drug or drug candidate. Using the normal cell culture plate, co-culture methods are achieved by mixing the different cell types or by the use of membranes to allow two cell types to be cultured on both sides of the membrane. Evaluation of the individual cell types after being physically mixed or by using membranes can be highly difficult and tedious. Thus, a need exists for a new cell culture tool that facilitates cell co-culturing.